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Introduction Patients treated with Immunocheckpoint Inhibitors (ICI) can develop adverse cardiovascular events, most frequently myocarditis, but also arrhythmias, conduction abnormalities, pericarditis, Takotsubo syndrome, ACS, heart failure, cardiac arrest. Myocarditis occurs early, within the first 3–4 administrations of therapy, and is fraught with a high mortality rate. Case Presentation 80–year–old patient with renal pelvic carcinoma who underwent nephroureterectomy and subsequent adrenalectomy. Twenty days after the first cycle of Pembrolizumab, the patient is admitted to cardiology for syncope and ECG finding of Left Posterior Fascicular Block (LPFB) and right bundle branch block (RBBB) with significant increase in troponin without any alterations in regional kinetics and normal ventricular function (EF). The patient also complains of widespread muscle pain and severe hyponatremia on blood tests. On ECG monitoring, alternation of RBBB with associated LPFB and Left Posterior Fascicular Block, left bundle branch block, first and second degree atrio–ventricular block (AV block) and on day II appearance of complete paroxysmal AV block controlled with temporary pacemaker implantation. On the 4th day, we documented changes in the segmental motion of the left ventricle (LV) and progressive gradual worsening of the EF. During the hospitalization the patient manifested episodes of general malaise with profuse sweating and marked hypotension with possible SIADH picture. In suspicion of acute myocarditis, peripheral myositis and possible Pembrolizumab SIADH, the patient was treated with high dose methylprednisolone (1000 mg / day) with little benefit. On the 6th day the patient was found in critical condition, severely suffering, hypotensive and oliguric, resigned herself. Conclusions Our case highlights how even a single dose of Pembrolizumab can trigger an acute inflammatory pattern affecting the myocardium with prevalent involvement of the conduction tissue even before the appearance of alterations in the kinetics and ventricular dysfunction. During ICI therapy cycles it is therefore important to monitor the ECG and troponin levels in order to be able to diagnose myocardial involvement early. In fact, although this complication is rare, it is burdened by a high mortality rate. The only treatment currently available involves the suspension of immunotherapy and the administration of high–dose methylprednisolone.

Introduction Tako–Tsubo Syndrome (“TTS”) is a cardiomyopathy characterized by an acute reversible left ventricular dysfunction, mainly triggered by emotional or physical stress. Several variants have been reported, including reverse TTS, characterized by hypokinesia of basal segments and hyperkinesis of the apical ones. TTS has a clinical presentation similar to acute coronary syndrome but without evidence of obstructive coronary artery disease. A surprising association between TTS and cancer arose out of recent studies. Case Presentation 74–year–old patient got to the emergency room of our hospital for the appearance, apparently in the health, in the absence of physical or emotional stress of oppressive chest pain. On the ECG, there was evidence of ST–segment elevation in inferior leads, for which urgent coronary angiography was performed. It did not show significant stenotic lesions nor evidence of elevated troponin values. The Echocardiogram showed hypokinesia of the basal segments and hyperkinesis of the mid–apical ones, with EF 40%. In the following days, the patient performed MRI–heart with detection of LGE of the intramyocardial type (non–ischemic pattern) in correspondence with the inferior wall in the medioventricular area. During hospitalization on routine chest x–ray, hypodiaphanous image was found in the left apex for which an HR CT scan of the chest was performed which a lesion in the left apical lung area with spiculated margins of a heteroplastic nature, associated with multiple bilateral lesions suggestive of secondaryism. Therefore, the patient was taken over by the Oncology service. Conclusions Such case confirms the association between TTS and occult cancer. In the absence of obvious physical or emotional stress that may explain the onset of TTS, it is important to research for any silent neoplastic pathology. The literature shows that the prevalence of malignant diseases is high in patients with TTS. Recent studies have pinpointed the activation of the sympathetic nervous system promotes cardiac inflammation by upregulating ICAM–1 and the expression of p53. Furthermore, inflammation can lead to the activation of p38 MAP Kinase, thus contributing to myocardial stunning. The specific role of inflammation as a cofactor of adrenaline–induced stunning deserves further investigation in the specific context of malignant tumors, which are frequently associated with an enhanced inflammatory state.